Search Results (29)

Detecting highly divergent or previously unknown viruses is a critical bottleneck in clinical diagnostics and pathogen surveillance. While alignment-based methods often fail to classify sequences lacking homology to known references, deep learning offers a powerful alternative for signal extraction from ‘viral dark matter.’ In this work, we present a high-performance ensemble of deep convolutional neural networks specifically designed to identify viral contigs in complex human metagenomic datasets. Our framework processes sequences acquired from high-throughput biological sensors and integrates complementary architectures to capture both local motifs and global genomic signatures. The proposed ensemble achieves state-of-the-art performance, reaching an AUROC of 0.939 on 300 bp contigs and significantly outperforming existing models such as transformer-based approaches, ViraMiner, and DeepVirFinder. Crucially, our results demonstrate high robustness to data degradation, maintaining stable predictive power even with a 10% random nucleotide substitution rate, a common challenge in degraded clinical samples. Furthermore, the model generalizes to ‘unseen’ viral families not present during training, demonstrating its utility for emerging threat detection. To ensure full reproducibility and facilitate further research in clinical sensing, the complete code and datasets are publicly available on Github. Full article

Chronic lymphocytic leukemia (CLL) is uncommon in Asia, and longitudinal genomic data from Asian cohorts are limited. We conducted serial whole-exome sequencing (WES) in a multicenter Korean cohort of newly diagnosed, elderly CLL treated with chlorambucil–obinutuzumab to evaluate mutational heterogeneity and clonal hematopoiesis of indeterminate potential (CHIP) during treatment and follow-up. Tumor-only variants were filtered, restricted to nonsynonymous or loss-of-function coding/splice-site mutations, and summarized as a binary patient-by-gene matrix for principal component analysis (PCA), trajectory analysis, and k-means clustering. CHIP was defined as ≥1 qualifying mutation in a prespecified CHIP gene set. Baseline PCA was more compact in patients with complete response at end of treatment, whereas partial response or progressive disease cases were more dispersed. PCA trajectories were compact and directionally consistent in complete responders, more dispersed in partial responders, and highly heterogeneous without a dominant direction in progressive disease. Clustering identified dispersed and compact clusters, and CHIP-associated mutations were enriched in the dispersed cluster (55.6% vs. 8.3%, Fisher’s exact p = 0.0086). In paired samples collected 3–5 months after end of treatment, CHIP status changed in some patients. Serial WES may provide complementary information to treatment response, although these observations require confirmation in larger cohorts. Full article

Nationwide hospital discharge databases are increasingly used in infectious disease research, yet their methodological strengths and limitations are rarely synthesised. In Spain, the Minimum Basic Data Set (Conjunto Mínimo Básico de Datos, CMBD) was implemented in 1987 and provides near-universal coverage of acute-care hospitalisations and has been widely applied in infectious disease epidemiology. However, its overall contribution and intrinsic constraints have not been comprehensively mapped. Given the breadth of infections, study designs, populations and outcome definitions in CMBD-based research, effect-size synthesis was not feasible; therefore, we conducted a scoping review with an evidence-mapping approach. We aimed to synthesise the scope, applications and methodological limitations of CMBD-based infectious disease research since its implementation. We conducted a scoping review following JBI guidance and reported according to PRISMA-ScR. PubMed, Embase, Web of Science and Scopus were searched from inception to 25 November 2024 for peer-reviewed journal articles in English or Spanish using CMBD data to investigate infectious diseases in Spain (no restrictions were applied by study design; grey literature was excluded). Screening, data charting and synthesis were completed during 2025. Four reviewers independently screened records and charted data. Studies were classified by infectious disease focus, syndromic category, study design and geographical scope. A total of 359 studies published between 1996 and 2024 were included, mostly retrospective observational analyses. Infectious diseases were the primary focus in 225 studies (62.7%), most commonly respiratory, gastrointestinal/liver and vaccine-preventable infections. Subnational analyses were concentrated in a limited number of regions. Over 80% of reported limitations reflected intrinsic CMBD features. Over three decades, the CMBD has become a cornerstone of hospital-based infectious disease research in Spain, enabling robust national analyses. However, limitations in clinical detail, microbiological confirmation and coding consistency constrain aetiological specificity and causal inference, highlighting the need for data validation and linkage with complementary sources. Full article

This study presents an in silico proof of concept exploring whether deep learning models can perform conditional mitochondrial DNA (mtDNA) sequence prediction across species boundaries. A CNN–BiLSTM model was trained under a leave-one-species-out (LOSO) scheme on complete mitochondrial genomes from 21 vertebrate species, primarily archosaurs. Model behavior was evaluated through multiple complementary tests. Under context-conditioned settings, the model performed next-nucleotide prediction using overlapping 200 bp windows to assemble contiguous 2000 bp fragments for held-out species; the resulting high token-level accuracy (>99%) under teacher forcing is reported as a diagnostic of conditional modeling capacity. To assess leakage-free performance, a two-flank masked-span imputation task was conducted as the primary evaluation, requiring free-running reconstruction of 500 bp interior spans using only distal flanking context; in this setting, the model consistently outperformed nearest-neighbor and demonstrated competitive performance relative to flank-copy baselines. Additional robustness analyses examined sensitivity to window placement, genomic region (coding versus D-loop), and random initialization. Biological plausibility was further assessed by comparing predicted fragments to reconstructed ancestral sequences and against composition-matched null models, where observed identities significantly exceeded null expectations. Using the National Center for Biotechnology Information (NCBI) BLAST web interface, BLASTn species identification was performed solely as a biological plausibility check, recovering the correct species as the top hit in all cases. Although limited by dataset size and the absence of ancient DNA damage modeling, these results demonstrate the feasibility of conditional mtDNA sequence prediction as an initial step toward more advanced generative and evolutionary modeling frameworks. Full article

Molecular chaperones, especially heat shock proteins (HSPs) have vital functions in cells’ responses to stress. Here, we cloned and sequenced the complete complementary DNA encoding HSP90 (MjHSP90) from the shrimp Marsupenaeus japonicus. The MjHSP90 cDNA comprised 3162 bp, including a 2172 bp coding region encoding a 724 amino acid-protein (predicted molecular mass = 83.12 kDa). Homology and phylogenetic analyses showed that MjHSP90 was highly conserved and most homologous to Litopenaeus vannamei HSP90. MjHSP90 is expressed in all tested tissues, with high expression in gill tissue and the hepatopancreas. Cold stress significantly upregulated MjHSP90 expression in the gill and hepatopancreas (p < 0.05). Following RNA interference knockdown of MjHSP90, the cold stress-related death rate of the shrimp increased significantly, accompanied by significantly upregulated expression of apoptosis-related genes Mjcaspase-3 and Mjbcl-2 (p < 0.05) and an increase in the number of apoptotic cells. The results indicated that MjHSP90 might play a pivotal role in the shrimp’s immune response to cold stress. Full article

The transition of cities towards a smarter approach significantly benefits from citizen participation in the development and implementation of innovative information and communication technology (ICT) products and services. Despite the emergence of various initiatives in recent years aimed at guiding the development of smart cities, there is still a lack of effective strategies to actively engage citizens, businesses, and educational institutions during the creation of these products and services. This study describes a set of practices that includes four co-creation techniques to facilitate the effort of software system development in collaboration with citizens and other stakeholders. The SEMAT standard is used to create and represent a method in which these practices are distributed across four stages: focus, definition, development, and validation. In each stage, a practice is proposed that incorporates a co-creation technique and complementary activities from various software engineering disciplines to promote active citizen participation; stimulate idea generation; and facilitate the creation of necessary documents and components for the development of the desired software system, including design systems, code files, conceptual representations, and technical diagrams, among others. Finally, the applicability and completeness of the method are validated through expert consultation in the fields of software engineering and smart cities. Recognized procedures are followed to obtain qualitative and quantitative results, such as improvement actions (addition or removal of elements), levels of consensus or acceptance, and opportunities for future work. Full article

Background. Tulipa species are economically, culturally, scientifically, and ecologically important. Tulips present taxonomic complexities that cannot be adequately resolved by examining their morphological characteristics alone or by relying on a limited selection of genetic markers. Methods. In the present study, we assessed the complete plastid sequences of Tulipa alberti Regel and Tulipa greigii Regel collected from Kazakhstan. Additionally, 14 previously published plastomes were obtained from GenBank for comparison and phylogenetic analysis. Results. The plastid genome sizes of T. alberti and T. greigii were 152,359 bp and 152,242 bp, respectively. In the plastid genomes of T. alberti and T. greigii, 136 genes were annotated, 114 of which were unique. These unique genes comprised eighty protein-coding, thirty transfer RNA, and four ribosomal RNA genes. Additionally, 415 simple sequence repeats were identified, comprising 107 tandem, 40 forward, 49 palindromic, 8 reverse, and 1 complementary repeat. Notably, the region containing ycf1 exhibited high variability and may serve as an informative DNA barcode for this genus. Conclusion. Phylogenetic analysis showed strong support for the relationships among Tulipa species, indicating the utility of plastid genome data for further taxonomic studies within the genus. Full article

Waveform design for integrated radar and jamming is generally based on the concept of shared waveform, which uses jamming signals without typical radar signal characteristics for detection. Existing waveforms have shown limited design flexibility, high levels of sidelobe in detection results, and overall ordinary performance. We propose an integrated radar and jamming waveform based on smart modulation and complementary coding. Unlike traditional integrated radar and jamming waveform based on smart modulation, the phase angle of the binary phase-coded sequence is adjustable in this smart modulation method, allowing for a controllable jamming effect, achieving true smart modulation. However, this smart modulation waveform also suffers from high sidelobes in detection. To address this issue, we take a complementary coding approach and design a smart modulation waveform with complementary characteristics. This waveform can synthesize a complete linear frequency modulation (LFM) signal by adding two pulses together, thereby reducing the sidelobes in the smart modulation waveform and enhancing its detection performance. Theoretical analysis indicates that the detection and jamming effects of this integrated waveform can be flexibly controlled by adjusting the phase angles of the coding sequences. Simulation analysis and experimental results confirm the significant advantages of this waveform. Full article

The Trusted Execution Environment (TEE) is designed to establish a safe environment that prevents the execution of unauthenticated programs. The nature of TEE is a continuous verification process with hashing, signing, and verifying. Such a process is called the Chain-of-Trust, derived from the Root-of-Trust (RoT). Typically, the RoT is pre-programmed, hard-coded, or embedded in hardware, which is locally produced and checked before booting. The TEE employs various cryptographic processes throughout the boot process to verify the authenticity of the bootloader. It also validates other sensitive data and applications, such as software connected to the operating system. TEE is a self-contained environment and should not serve as the RoT or handle secure boot operations. Therefore, the issue of implementing hardware for RoT has become a challenge that requires further investigation and advancement. The main objective of this proposal is to introduce a secured RISC-V-based System-on-Chip (SoC) architecture capable of securely booting a TEE using a versatile boot program while maintaining complete isolation from the TEE processors. The suggested design has many cryptographic accelerators essential for the secure boot procedure. Furthermore, a separate 32-bit MicroController Unit (MCU) is concealed from the TEE side. This MCU manages sensitive information, such as the root key, and critical operations like the Zero Stage BootLoader (ZSBL) and key generation program. Once the RoT is integrated into the isolated sub-system, it becomes completely unavailable from the TEE side, even after booting, using any method. Besides providing a secured boot flow, the system is integrated with essential crypto-cores supporting Transport Layer Security (TLS) 1.3. The chip is finally fabricated using the Complementary Metal–Oxide–Semiconductor (CMOS) 180 nm process. Full article

Antisense long noncoding RNA (as-lncRNA) is a lncRNA transcribed in reverse orientation that is partially or completely complementary to the corresponding sense protein-coding or noncoding genes. As-lncRNAs, one of the natural antisense transcripts (NATs), can regulate the expression of their adjacent sense genes through a variety of mechanisms, affect the biological activities of cells, and further participate in the occurrence and development of a variety of tumours. This study explores the functional roles of as-lncRNAs, which can cis-regulate protein-coding sense genes, in tumour aetiology to understand the occurrence and development of malignant tumours in depth and provide a better theoretical basis for tumour therapy targeting lncRNAs. Full article

Torix tukubana is a poorly understood proboscidate leech species, generally an ectoparasite on amphibian species. In this study, the complete mitochondrial genome (mitogenome) of T. tukubana was sequenced using next-generation sequencing (NGS), and the essential characteristics, gene arrangement, and phylogenetic relationship were analyzed. The results showed that the T. tukubana mitogenome was 14,814 bp in length, consisting of 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and 1 control region (CR). The mitogenome composition presented a strong A + T bias (73.6%). All tRNAs had the typical clover structure except the trnS1 (TCT), whose dihydrouridine (DHU) arm was short, having only one complementary base pair. Additionally, 8 gene order patterns were identified among 25 known Hirudinea species, and T. tukubana was identical to the Hirudinea ground pattern. A phylogenetic analysis based on 13 PCGs indicated that all the studied species clustered into three main clades. The relationships among Hirudinea species were basically consistent with their gene arrangement results, but different from their morphological taxonomy. T. tukubana was in the monophyletic group of Glossiphoniidae, a finding consistent with previous research. Our results provided the essential characteristics of the T. tukubana mitogenome. As the first complete mitogenome of Torix, it could offer valuable information for a systematic understanding of the Hirudinea species. Full article

This paper reports the first complete sequence of the mitochondrial genome (mitogenome) of the yellow-striped flounder Pseudopleuronectes herzensteini (Pleuronectoidei: Pleuronectidae). Mitogenome evolution, and molecular phylogenetic reconstruction based on four to six techniques, including coalescent analysis, were performed for flatfish. The genome size of the specimen sampled was 16,845 bp, including 13 protein-coding genes, 22 tRNA genes, 12S, and 16S rRNA genes, and the control region, CR. The composition and arrangement of the genes are similar to those in other teleost fish, including the second mitogenome reported in this paper. The frequency of A, C, G, and T nucleotides in the P. herzensteini mitogenome is 27%, 29.2%, 17.6%, and 26.2%, respectively. The ratio of complementary nucleotides in the mitogenome of this and other species of the family was A+T:G+C (53.2: 46.8%) and do not deviate significantly from the expected equilibrium proportion. The submission to the global database (GenBank) of two new mitogenomes along with 106 analyzed GenBank sequences will contribute to phylogenetic studies of flounders at the family and suborder levels. Based on 26 and 108 nucleotide sequences of protein-coding genes (PCGs), we investigated the molecular phylogeny of flounders and performed analysis for two sets of sequences, including those of members of the family Pleuronectidae and the suborder Pleuronectoidei and estimated their importance in establishing the taxonomy at these two levels. Data obtained by up to six techniques of multigene phylogenetic reconstructions support monophyly within the family Pleuronectidae with high statistical confidence; however, conclusions regarding the phylogenetics at the suborder level require further investigation. Our results also revealed paraphyletic and weakly supported branches that are especially numerous at the suborder level; thus, there is a clear need for taxonomic revisions at the suborder, and possibly family levels. Genetic distance analysis reveals the suitability for DNA barcoding of species specimens at single genes as well as at whole mitogenome data. Full article

The Chinese white wax scale, Ericerus pela, is an insect native to China. It harbors a variety of microbes. The Paraconiothyrium fungus was isolated from E. pela and genome sequenced in this study. A fungal cytotoxicity assay was performed on the Aedes albopictus cell line C6/36. The assembled Paraconiothyrium sp. genome was 39.55 Mb and consisted of 14,174 genes. The coding sequences accounted for 50.75% of the entire genome. Functional pathway analyses showed that Paraconiothyrium sp. possesses complete pathways for the biosynthesis of 20 amino acids, 10 of which E. pela lacks. It also had complementary genes in the vitamin B groups synthesis pathways. Secondary metabolism prediction showed many gene clusters that produce polyketide. Additionally, a large number of genes associated with ‘reduced virulence’ in the genome were annotated with the Pathogen–Host Interaction database. A total of 651 genes encoding carbohydrate-active enzymes were predicted to be mostly involved in plant polysaccharide degradation. Pan-specific genomic analyses showed that genes unique to Paraconiothyrium sp. were enriched in the pathways related to amino acid metabolism and secondary metabolism. GO annotation analysis yielded similar results. The top COG categories were ‘carbohydrate transport and metabolism’, ‘lipid transport and metabolism’, and ‘secondary metabolite biosynthesis, transport and catabolism’. Phylogenetic analyses based on gene family and pan genes showed that Paraconiothyrium sp is clustered together with species from the Didymosphaeriaceae family. A multi-locus sequence analysis showed that it converged with the same branch as P. brasiliense and they formed one group with fungi from the Paraconiothyrium genus. To validate the in vitro toxicity of Paraconiothyrium sp., a cytotoxicity assay was performed. The results showed that medium-cultured Paraconiothyrium sp. had no harmful effect on cell viability. No toxins were secreted by the fungus during growth. Our results imply that Paraconiothyrium sp. may establish a symbiotic relationship with the host to supply complementary nutrition to E. pela. Full article

Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies. Full article

Cardiovascular development is a complex process that starts with the formation of symmetrically located precardiac mesodermal precursors soon after gastrulation and is completed with the formation of a four-chambered heart with distinct inlet and outlet connections. Multiple transcriptional inputs are required to provide adequate regional identity to the forming atrial and ventricular chambers as well as their flanking regions; i.e., inflow tract, atrioventricular canal, and outflow tract. In this context, regional chamber identity is widely governed by regional activation of distinct T-box family members. Over the last decade, novel layers of gene regulatory mechanisms have been discovered with the identification of non-coding RNAs. microRNAs represent the most well-studied subcategory among short non-coding RNAs. In this study, we sought to investigate the functional role of distinct microRNAs that are predicted to target T-box family members. Our data demonstrated a highly dynamic expression of distinct microRNAs and T-box family members during cardiogenesis, revealing a relatively large subset of complementary and similar microRNA–mRNA expression profiles. Over-expression analyses demonstrated that a given microRNA can distinctly regulate the same T-box family member in distinct cardiac regions and within distinct temporal frameworks, supporting the notion of indirect regulatory mechanisms, and dual luciferase assays on Tbx2, Tbx3 and Tbx5 3′ UTR further supported this notion. Overall, our data demonstrated a highly dynamic microRNA and T-box family members expression during cardiogenesis and supported the notion that such microRNAs indirectly regulate the T-box family members in a tissue- and time-dependent manner. Full article